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Comparative antihypertensive and renoprotective effects of telmisartan and lisinopril after long-term treatment in hypertensive diabetic rats

Department of Pharma Research, Boehringer Ingelheim Pharma KG, Biberach, Germany, wienen{at}bc.boehringer-ingelheim.com

Serge Richard

Centre de Recherches Biologiques, 18800 Baugy, France

Pascal Champeroux

Centre de Recherches Biologiques, 18800 Baugy, France

Chantal Audeval-Gerard

Centre de Recherches Biologiques, 18800 Baugy, France

This study compared the cardiovascular and renal effects of long-term telmisartan (3 and 10 mg/kg/day) and lisinopril (10 mg/kg/day) in an animal model combining hypertension and diabetes mellitus.

It was a parallel-group study of diabetic, spontaneously hypertensive rats (SHR), treated with control or active treatment for eight months. A non-diabetic SHR control group was run in parallel. Diabetes was induced by streptozotocin (45 mg/kg i.v.) in SHRs aged 9—10 weeks. Animals were treated with telmisartan (3 or 10 mg/kg/day), lisinopril (10 mg/kg/day) or vehicle. Plasma glucose levels, blood pressure (BP), and urinary protein and albumin excretion were measured monthly. Telmisartan treatment significantly reduced BP of diabetic SHRs in a dose-dependent manner (p<0.05, low-dose, n=18; p<0.01, high-dose, n=15). The BP reduction in the lisinopril group was similar to that in the telmisartan 10 mg/kg/day group. Compared with non-diabetic SHRs, untreated diabetic SHRs developed severe proteinuria and albuminuria over the experimental period (p<0.01). In diabetic SHRs, proteinuria and albuminuria were dose-dependently and significantly attenuated by treatment with telmisartan (p<0.01 with the higher dose) and lisinopril (p<0.01). Compared with the untreated diabetic SHRs, cardiac hypertrophy was significantly reduced after treatment with both doses of telmisartan and with lisinopril. Telmisartan, 10 mg/kg/ day, but not lisinopril, significantly attenuated the diabetes-induced increase in glomerular volume. In conclusion, telmisartan, 10 mg/kg/day, is at least as beneficial as lisinopril, 10 mg/kg/day, in lowering BP, reducing cardiac hypertrophy and attenuating renal excretion of protein and albumin in this model.

Key Words: telmisartan • lisinopril • antihypertensive • hypertension • diabetes • renoprotection • angiotensin II receptor antagonist

References

• Stamler J., Vaccaro O., Neaton JD, Wentworth D. Diabetes, other risk factors, and 12-yr cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial. Diabetes Care 1993;16:434-44.[Abstract]
• Haffner SM, Lehto S., Ronnemaa T., Pyorala K., Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med 1998;339:229-34.[Abstract/Free Full Text]
• Jelesoff NE, Feinglos M., Granger CB, Califf RM Outcomes of diabetic patients following acute myocardial infarction: a review of the major thrombolytic trials. J Cardiovasc Risk 1997;4:100-11.[CrossRef][Medline] [Order article via Infotrieve]
• Parving HH, Tarnow L., Rossing P. Renal protection in diabetes - an emerging role for calcium antagonists. Cardiology 1997;88(suppl 3):56-62.[CrossRef]
• Parving HH, sterby R., Anderson PW, Hsueh WA Diabetic nephropathy. In: Brenner BM (ed) The Kidney 5th edition. Philadelphia:Saunders 1996: 1864-92.
• Hansson L., Zanchetti A., Carruthers SG et al. Effects of intensive blood pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomized trial. Lancet 1998;351:1755-62.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ 1998;317:703-13.[Abstract/Free Full Text]
• Lewis EJ, Hunsicker LG, Bain RP, Rohde RD and the Collaborative Study Group. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. N Engl J Med 1993;329:1456-62.[Abstract/Free Full Text]
• Crepaldi G., Carraro A., Brocco E., Adezati L., Andreani D., Bompiani G. Hypertension and non-insulin-dependent diabetes.Acta Diabetol 1995;32:203-8.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Velussi M., Brocco E., Frigato F., Zolli M., Muollo B., Maioli M. Effects of cilazapril and amlodipine on kidney function in hypertensive NIDDM patients. Diabetes 1996;45:216-22.[Abstract]
• Bakris GL, Copley JB, Vicknair N., Sadler R., Leurgans S. Calcium channel blockers versus other antihypertensive therapies on progression of NIDDM associated nephropathy. Kidney Int 1996;50:1641-50.[Web of Science][Medline] [Order article via Infotrieve]
• WienenW, Hauel N., van Meel JC, Narr B., Ries U., Entzeroth M. Pharmacological characterization of the novel nonpeptide angiotensin II receptor antagonist, BIBR 277. Br J Pharmacol 1993;110:245-52.[Web of Science][Medline] [Order article via Infotrieve]
• Böhm M., Lee M., Kreutz R. et al. Angiotensin II receptor blockade in TGR(mREN2)27: effects of renin-angiotensin-system gene expression and cardiovascular functions. Hypertension 1995;13:891-9.[CrossRef]
• Böhm M., Lippoldt A., Wienen W., Ganten D., Bader M. Reduction of cardiac hypertrophy in TGR(mREN2)27 by angiotensin II receptor blockade. Mol Cell Biochem 1996;163/164:217-21.
• Wagner J., Drab M., Bohlender J., Amann K., Wienen W., Ganten D. Effects of AT1 receptor blockade on blood pressure and the renin-angiotensin system in spontaneously hypertensive rats of the stroke prone strain. Clin Exp Hypertens 1998;20:205-21.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• WienenW, Entzeroth M. Effects on binding characteristics and renal function of the novel, non-peptide angiotensin II antagonist BIBR 277 in the rat. J Hypertens 1994;12:119-28.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Weibel ER Stereological Methods: Practical Methods for Biological Morphometry. London:Academic Press Inc 1979:51-7.
• Marsden PA, Brenner BM, Ballermann BJ Mechanisms of angiotensin action on vascular smooth muscle, the adrenal and the kidney. In: Laragh JH, Brenner BM (eds) Hypertension. New York: Raven Press 1990:1247-71.
• Black MJ, Briscoe T., Bertram JF, Jackson B. Cardiac hypertrophy in diabetic spontaneously hypertensive rats: role of angiotensin II? Clin Exp Pharmacol Physiol 1997;24:445-8.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Rumble JR, Doyle,AE Cooper ME Comparison of effects of ACE inhibition with calcium channel blockade on renal disease in a model combining genetic hypertension and diabetes. Am J Hypertens 1995;8:53-7.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Kohzuki M., Yasujima M., Kanazawa M. et al. Antihypertensive and renal-protective effects of losartan in streptozotocin diabetic rats. J Hypertens 1995;13:97-103.[Web of Science][Medline] [Order article via Infotrieve]
• Cooper ME, Allen TJ, O'Brien RC et al. Effects of genetic hypertension on diabetic neuropathy in the rat - functional and structural characteristics.J Hypertens 1988;6:1009-16.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Cooper ME, Allen TJ, Macmillan P.,Bach L., Jerums G., Doyle AE Genetic hypertension accelerates nephropathy in the streptozotocin diabetic rat. Am J Hypertens 1988;1:5-10.[Web of Science][Medline] [Order article via Infotrieve]
• Neutel JM, Frishman WH, Oparil S., Papademitriou V., Guthrie G. Comparison of telmisartan with lisinopril in patients with mild-to-moderate hypertension.AmJTher 1999;6:161-6.
• Lacourcière Y., and the Telmisartan Cough Study Group. The incidence of cough: a comparison of lisinopril, placebo and telmisartan, a novel angiotensin II antagonist. Int J Clin Pract 1999;53:99-103.[Web of Science][Medline] [Order article via Infotrieve]
• Parving HH Renoprotective action of angiotensin-converting enzyme inhibition in diabetes mellitus. J Cardiovasc Pharmacol 1992;19:S19-S24.[Web of Science][Medline] [Order article via Infotrieve]
• Ravid M., Lang R., Rachmani R., Lishner M. Long-term renoprotective effect of angiotensin-converting enzyme inhibition in non-insulin-dependent diabetes mellitus. A 7-year follow-up study. Arch Intern Med 1996;156:286-9.[Abstract/Free Full Text]
• Kasiske BL, Kalil RS, Ma JZ, Liao M., Keane WF Effect of antihypertensive therapy on the kidney in patients with diabetes: a meta-regression analysis. Ann Intern Med 1993;118:129-38.[Abstract/Free Full Text]

Journal of Renin-Angiotensin-Aldosterone System, Vol. 2, No. 1, 31-36 (2001)
DOI: 10.3317/jraas.2001.005


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This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Wienen, W. Articles by Audeval-Gerard, C. Search for Related Content PubMed PubMed Citation Articles by Wienen, W. Articles by Audeval-Gerard, C. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Blood Pressure Medicines High Blood Pressure Hazardous Substances DB LISINOPRIL Social Bookmarking                         What's this?